HSV-1 infections are common and affect between 70 and 80 percent of the total population in the United States. Several manifestations of HSV disease cause significant morbidity and mortality. For example, HSV disease in an immunocompromised host will often result in progressive infection, particularly in stem cell transplant recipients. HSV infection is also a risk factor in HIV infection and transmission. HSV-1 is a human pathogen responsible for localized mucocutaneous lesions and encephalitis, and is transmitted via body secretions and/or direct oral and sexual contact.
During infection of a cell, expression of HSV proteins interferes with the induction of antiviral immunity. One such protein, the γ134.5 protein, consists of 263 amino acids and is essential in the pathogenesis of HSV infection. In the targeted/infected host cell, TBK1 is a key component of Toll-like receptor-dependent and -independent signaling pathways. In response to microbial components, TBK1 activates interferon regulatory factor 3 (IRF3) and cytokine expression.
While the γ134.5 protein of HSV-1 has been extensively studied and sequenced in various HSV strains, there is scant evidence to show how the γ134.5 protein is a critical determinant of viral replication. Accordingly, effective use of the γ134.5 protein for treating HSV-related conditions and diseases has been slight. A method to identify compounds that can prevent or treat HSV-1 and HSV-2-related conditions and diseases is desired. Further, a γ134.5 protein-based vaccine having enhanced immunogenicity over other HSV-1 related vaccines is also desired.